Nesiritide and Renal Function After the Total Artificial Heart
The Impact of Nesiritide on Renal Function After Implantation of the Total Artificial Heart and Left Ventricular Assist Devices
調査の概要
詳細な説明
This is a randomized, double blinded placebo controlled study that will take place in the Cardiac Surgery Intensive Care Unit, at Virginia Commonwealth University (VCU) Hospital Center.
This study will enroll 20 adult patients who have undergone implantation of a circulatory support device (10 TAH patients, 10 Left ventricular assist device (LVAD) patients). Patients will receive standard postoperative care, including anticoagulation, continuous hemodynamic monitoring with an arterial line and central venous line and hemodynamic support as determine by the cardiac surgery clinical team. We will exclude patients who are receiving renal replacement therapy at the time of device implantation or those that have had previous solid organ transplantation in order to remove the confounding influence of calcineurin inhibitor exposure on renal function. Patient unable to provide informed consent will also be excluded.
Nesiritide Infusion
The patients will be randomized (stratified by device type) to either the study drug (nesiritide at 0.005 mcg/kg/min without a bolus) or placebo. A fixed-dose infusion will be initiated 6 hours after the patients having come off of cardiopulmonary bypass and continued for 48 hours.
Laboratory Measurements
Acute and chronic effects of nesiritide on Glomerular Filtration Rate (GFR) and Renal Plasma Flow (RPF) will be measured by continuous infusion of iothalamate (IOTH) and phenylalanine hydroxylase (PAH), respectively. GFR and RPF will be measured at baseline (-3 to 0 hrs) and at 3 intervals during drug/placebo administration as follows: 0 to 6, 6 to 16 and 16 to 40. Intravenous catheters will be placed as needed for infusion of PAH and IOTH and for timed blood collections.
Urine volume, creatinine, sodium excretion will also be measured. Neurohormones will be measured at all time points 3-6. Plasma renin activity will be measured with an automated chemiluminescent immunoassay (DiaSorin Liaison). Serum aldosterone concentration will be determined by liquid chromatography-mass spectrometry (Agilent, AB Sciex API 5000). Serum BNP concentration will be measured with a sandwich chemiluminescent immunoassay (Siemens Healthcare Diagnostics, ADVIA Centaur BNP immunoassay).
Statistical Analysis Sample size was determined using urine output data from our preliminary observations. Power calculations showed that a total of 10 patients in this two-treatment parallel-design study to have 84 percent power to detect a change in urine output by 75 mL/hr at a two-sided 0.05 significance level (using standard deviation of 35 mL/hr for urine output). Thus 10 patient were included in each device arm of the study.Chi-square analysis was used to compare discrete variables.
A two tailed Student's t-test was used to compare continuous variables. A repeated measures analysis of variance (ANOVA) was used to compare changes in clinical variables laboratory measurements across time points. A P value < 0.05 was considered significant. For individual comparisons post-hoc testing was performed with a paired t-test analysis with Bonferroni correction for 2 comparisons and thus only a P value < 0.025 will considered significant for the repeated measures analyses. A Student 2-tailed paired t test will be used to compare placebo and active drug values for each individual time point.
研究の種類
入学 (実際)
段階
- フェーズ 4
連絡先と場所
研究場所
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Virginia
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Richmond、Virginia、アメリカ、23298
- Virginia Commonwealth University Medical Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Implanted with a total artificial heart (CardioWest) or Left ventricular assist device (HeartMate II)
- Age > 18 years
Exclusion Criteria:
- Previous calcineurin inhibitor (CNI) exposure
- Hemodialysis prior to device implant
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Total Artificial Heart
Nesiritide
|
nesiritide at 0.005 mcg/kg/min without a bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.
他の名前:
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プラセボコンパレーター:Total Artificial Heart: Placebo
Control arm for subjects receiving the Total Artificial Heart and randomized to receive placebo
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placebo bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.
|
アクティブコンパレータ:LVAD: Nesiritide
Active arm of the LVAD group
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nesiritide at 0.005 mcg/kg/min without a bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.
他の名前:
|
プラセボコンパレーター:LVAD: Placebo
Control arm for subjects receiving LVAD and randomized to placebo
|
placebo bolus starting 6 hours after the subject has come off of cardiopulmonary bypass and will continue for 48 hours.
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
---|---|
Glomerular Filtration Rate
時間枠:46 hours
|
46 hours
|
Renal Plasma Flow
時間枠:46 Hours
|
46 Hours
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二次結果の測定
結果測定 |
時間枠 |
---|---|
Need for Hemodialysis/Renal Replacement Therapy
時間枠:90 days
|
90 days
|
Urine Output
時間枠:46 Hours
|
46 Hours
|
Time to Renal Failure
時間枠:46 Hours
|
46 Hours
|
Total Diuretic Requirement
時間枠:46 Hours
|
46 Hours
|
協力者と研究者
捜査官
- 主任研究者:Keyur B. Shah, MD、Virginia Commonwealth University Medical Center
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
うっ血性心不全の臨床試験
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Novartis Pharmaceuticals完了EC-MPS による治療に関心があり、コア研究の 12 か月の治療期間を無事に完了した患者 (de novo Heart Recipients)